Thalassemia Overview and Types

Study Notes

Thalassemia

A group of genetic blood disorders characterized by reduced or absent synthesis of globin chains in hemoglobin.
Thalassa: Greek word for "sea" - First observed in Mediterranean populations.
Most common single-gene disorder.
Autosomal recessive inheritance - both parents must carry the gene for offspring to be affected.

Types of Thalassemia

Beta Thalassemia: Point mutations on chromosome 11, leading to reduced or absent beta-globin chain production.
Alpha Thalassemia: Gene deletions on chromosome 16, resulting in reduced or absent alpha-globin chain synthesis.

Pathophysiology

Reduced beta-globin production leads to increased production of HbF (α2γ2) and HbA2 (α2 δ2) to compensate for the lack of HbA (α2 β2).
An excess of alpha globin chains forms aggregates, precipitating in red blood cells.
These aggregates (inclusion bodies) cause premature destruction of developing red blood cells in the bone marrow (ineffective erythropoiesis) and in the periphery (hemolysis).
The lack of sufficient HbA causes anemia and tissue hypoxia → stimulating erythropoiesis in the bone marrow and sometimes in other tissues (extramedullary hematopoiesis).

Clinical Manifestations in Thalassemia Major

Infants
- Often present between 6-9 months of age (as HbF is replaced by HbA).
- Progressive pallor and jaundice.
- Cardiac failure due to severe anemia.
- Growth failure and delayed development.
- Feeding difficulties, bouts of fever, and diarrhea.
- Hepatosplenomegaly (enlarged liver and spleen).
Childhood
- Growth retardation.
- Severe anemia requiring frequent blood transfusions.
- Jaundice.
- Characteristic skeletal changes.

Skeletal Changes in Thalassemia Major

Chipmunk Facies: Frontal bossing, maxillary hypertrophy (enlarged jaw), depression of the nasal bridge, and dental malocclusion.
Paravertebral Masses: Broad expansion of ribs at the vertebral attachment.
Paraparesis: Weakness or paralysis of the lower limbs.
Pathological Fractures: Cortical thinning and increased porosity of long bones due to bone marrow expansion.
Delayed Pneumatization of the Sinuses: Air-filled cavities in the skull develop later than expected.
Premature Fusion of Epiphyses: Short stature.

Other Clinical Features of Thalassemia Major

Delayed Menarche: Delayed onset of menstruation in females.
Gallstones: Obstructive jaundice due to gallstones.
Leg Ulcers: Associated with poor circulation.
Pericarditis: Inflammation of the sac surrounding the heart.
Diabetes: Iron deposition in the pancreas.
Cirrhosis of the Liver: Iron deposition in the liver.
Signs of Hypersplenism: Overactivity of the spleen, leading to low white blood cell counts.

Clinical Manifestations in Thalassemia Intermedia

Moderate Anemia: Hb levels usually above 6 gm/dL.
Worsening Anemia: Anemia worsens during pregnancy and infections.
Less Transfusion Dependent: Less frequent blood transfusions needed.
Skeletal Changes: Present but less pronounced.
Growth Retardation: Less severe.
Longer Survival: Better prognosis compared to Thalassemia major.

Clinical Manifestations in Thalassemia Minor

Usually Asymptomatic: Mild or no symptoms.
Mild Pallor: Slightly pale complexion.
No Jaundice, Growth Retardation, or Skeletal Abnormalities.
Splenomegaly
May Present as Iron Deficiency.

### Iron Overload
Iron released from red blood cell breakdown during the hemolytic process is not utilized for hemoglobin synthesis.
Iron accumulation (Hemosiderosis) can lead to complications:
- Hepatomegaly
- Hemochromatosis: Damage to the liver and other organs due to iron overload.
- Cardiac Hemosiderosis: Damage to the heart, including cardiomyopathy (weak heart muscle), pericarditis (inflammation of the heart sac), arrhythmias (irregular heartbeat), and heart block.
- Endocrine Disorders: Iron deposition in the pituitary gland can cause short stature, delayed puberty, and other hormone abnormalities.
- Diabetes Mellitus: Iron deposition in the pancreas.
- Lung Problems: Restrictive lung disease.
- Adrenal Insufficiency: Deficiency of hormones produced by the adrenal glands.
- Hypothyroidism and Hypoparathyroidism: Deficiencies of thyroid and parathyroid hormones.
- Increased Risk of Infections: Excess iron favors bacterial growth.
- Yersinia Infections: Commonly seen in Thalassemia patients.

Infections in Thalassemia

Increased susceptibility to infections due to various factors:
- Poor nutrition
- Iron overload
- Impaired immune system (monocyte and macrophage dysfunction).
- Hypersplenism leading to leukopenia (low white blood cell count).
- Infections associated with blood transfusions (Hepatitis B, C, and HIV)

Management of Thalassemia

Long-term management of thalassemia involves:
- Regular blood transfusions to maintain adequate hemoglobin levels.
- Iron chelation therapy to remove excess iron from the body.
- Supportive care, including folic acid supplementation, treatment for infections, and management of complications.
- Bone marrow transplant may be considered in some cases.

Important Points to Remember

Thalassemia is a genetic disorder affecting the production of globin chains in hemoglobin.
Symptoms can range from mild to life-threatening depending on the specific type and severity of the disorder.
Iron overload is a major complication of thalassemia, leading to organ damage and other health problems.
Treatment focuses on managing symptoms and improving quality of life.

Description

Explore the genetic blood disorder Thalassemia, characterized by the reduced synthesis of globin chains. Understand the distinctions between Beta and Alpha Thalassemia, their genetic causes, and the resulting pathophysiological effects. This quiz is designed to deepen your knowledge of these conditions and their impact on health.